ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.779G>A (p.Gly260Asp)

gnomAD frequency: 0.00009  dbSNP: rs148798048
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002530175 SCV000650787 benign Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2024-08-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002255455 SCV002533163 uncertain significance Dyskeratosis congenita 2021-11-22 criteria provided, single submitter curation
GeneDx RCV002260647 SCV002540303 uncertain significance not provided 2024-10-27 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in individuals with aplastic anemia or neuroblastoma (PMID: 19674077, 26580448, 30523342); Published functional studies demonstrate no damaging effect: no impact on telomere overhang length or binding with BRG-1 and beta-catenin (PMID: 19674077, 24983628); This variant is associated with the following publications: (PMID: 19674077, 24983628, 23716176, 30791107, 30523342, 26580448)
Baylor Genetics RCV003333079 SCV004041286 uncertain significance Aplastic anemia 2023-02-13 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV002260647 SCV005189389 uncertain significance not provided criteria provided, single submitter not provided
Ambry Genetics RCV002255455 SCV005512328 likely benign Dyskeratosis congenita 2024-08-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV005034105 SCV005669171 uncertain significance Acute myeloid leukemia; Dyskeratosis congenita, autosomal dominant 2; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1; Melanoma, cutaneous malignant, susceptibility to, 9 2024-06-08 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004735620 SCV005352537 uncertain significance TERT-related disorder 2024-08-19 no assertion criteria provided clinical testing The TERT c.779G>A variant is predicted to result in the amino acid substitution p.Gly260Asp. This variant has been reported in a 73 year old individual with acquired aplastic anemia (Calado et al. 2009. PubMed ID: 19674077), in an individual with neuroblastoma (TableS4b, Zhang et al. 2015. PubMed ID: 26580448), and in an individual with telomere disease (Kapuria et al. 2019. PubMed ID: 30791107). Functional studies have shown that this variant has no impact on telomere overhang length or protein binding (Calado et al. 2009. PubMed ID: 19674077; Zhang et al. 2014. PubMed ID: 24983628). This variant is reported in 0.071% of alleles in individuals of African descent in gnomAD. This variant has conflicting interpretations in ClinVar regarding is pathogenicity, ranging from uncertain to benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/471902). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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